PROJECT SUMMARY: UNIVERSITY OF PENNSYLVANIA (PENN) ALZHEIMER'S DISEASE (AD) CORE CENTER (ADCC) RENEWAL APPLICATION ADCC Director and Principal Investigator (PI): John Q. Trojanowski, MD, PhD ADCC Associate Directors: Jason Karlawish, MD and David Wolk, MD The Aims of the Penn ADCC are designed to achieve our mission of elucidating mechanisms underlying AD by focusing on the spectrum of disease from earliest onset through progressive stages of disease with the long term goal of accelerating the pace of developing better diagnostics and preventions/treatments for AD and related disorders (RD). To this end, the Specific Aims of this renewal application for the Penn ADCC are to: 1) oversee and direct the activities of the ADCC (Administrative Core A); 2) recruit, follow and study patients with AD, especially at their earliest stage, in addition to older cognitively normal subjects (CNs) with a strong emphasis on African-Americans (Clinical Core B and Outreach and Recruitment Core E); 3) provide data management, bioinformatics and biostatistical expertise for the multimodal integration of clinical, imaging, biomarker, genetic and neuropathology data on AD, as well as for cross-disease subtype comparisons bridging the entire spectrum of AD through data integration, data analyses and bioinformatics (Data Management, Biostatistics and Bioinformatics Core C); 4) establish postmortem diagnoses on ADCC patients, and bank AD and RD CNS tissues, DNA and biofluids for diagnostic studies and research to understand AD and RD pathophysiology, including mechanisms of disease progression, genetic factors influencing heterogeneity of AD expression, and the emergence of diverse strains of misfolded disease proteins (Neuropathology, Genetics and Biomarker Core D); 5) develop, implement, and monitor outreach, recruitment and retention programs that provide the ADCC team, patients and families, as well as our region with state-of-the-art knowledge about AD and associated co- morbid conditions that influence risk for cognitive decline, while ensuring that our research cohort reflects the ethnic and racial diversity of Penn's surrounding community (Outreach and Recruitment Core E); 6) Continue our Pilot Grant Program to stimulate novel research across the spectrum of AD and RD as well as normal aging through Core A which funds 2 pilots/year and Penn's Institute on Aging (IOA), which funds an additional 4-6 pilots/year; 7) Continue Collaborations with other investigators at and beyond Penn to improve understanding of and diagnostics and treatments for AD as well as educate and empower the community. 8) Increase our commitment since the launch of the Penn ADCC to train, mentor and nurture the next generation of researchers on AD, RD and healthy brain aging by implementing the new Research Education Component Core F. In summary, the Penn ADCC contributes to national and global strategies to meet the worldwide challenges of rapidly aging populations and the epidemic of AD and RD. By aligning with the current NIA RFA for ADCCs (RFA-AG-16-018), the Penn ADCC accomplishes its mission in the renewal period through research on AD, RD, mild cognitive impairment and healthy brain aging, as well as through education and outreach to increase understanding of these disorders and their global effects.